Clinical Trials Register

Summary
EudraCT Number:	2020-002688-77
Sponsor's Protocol Code Number:	D9720C00001
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-04-07
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2020-002688-77

A.3

Full title of the trial

A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination with Anti-cancer Agents in Patients with Advanced Solid Malignancies

Modulové, otevřené, multicentrické klinické hodnocení fáze I/IIa, jehož cílem je posoudit bezpečnost, snášenlivost, farmakokinetiku, farmakodynamiku a předběžnou účinnost zvyšujících se dávek přípravku AZD5305 použitého samostatně nebo v kombinaci s jinou léčbou proti rakovině jako léčba u pacientů s pokročilými solidními nádory (PETRA)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of AZD5305 as monotherapy and with anti-cancer agents in patients with advanced solid malignancies

A.4.1

Sponsor's protocol code number

D9720C00001

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04644068

A.5.4

Other Identifiers

Name:

EudraCT number

Number:

2020-002688-77

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca Clinical
B.5.2	Functional name of contact point	Study Information Center
B.5.3	Address:
B.5.3.1	Street Address	Not Applicable
B.5.3.2	Town/ city	Not Applicable
B.5.3.3	Post code	Not Applicable
B.5.3.4	Country	United States
B.5.5	Fax number	18772409479
B.5.6	E-mail	information.center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	AZD5305 film-coated tablets
D.3.2	Product code	AZD5305
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	2589531-76-8
D.3.9.2	Current sponsor code	AZD5305
D.3.9.3	Other descriptive name	N/A
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	0.5 to 100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Carboplatin
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Carboplatin
D.3.2	Product code	Not answered
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Carboplatin
D.3.9.1	CAS number	41575-94-4
D.3.9.2	Current sponsor code	carboplatin
D.3.9.3	Other descriptive name	N/A
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Paclitaxel
D.2.1.1.2	Name of the Marketing Authorisation holder	Bendatax
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Paclitaxel
D.3.2	Product code	Not answered
D.3.4	Pharmaceutical form	Infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Paclitaxel
D.3.9.1	CAS number	33069-62-4
D.3.9.2	Current sponsor code	Paclitaxel
D.3.9.3	Other descriptive name	N/A
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	5 to 100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced Solid Tumors

E.1.1.1

Medical condition in easily understood language

Cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10048683
E.1.2	Term	Advanced cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the safety and tolerability of AZD5305 as monotherapy and in combination with anti-cancer agents in patients with advanced malignancies

E.2.2

Secondary objectives of the trial

-To characterize the PK of AZD5305 in plasma following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents

- To assess the preliminary anti-tumour activity of AZD5305 as monotherapy and in combination with anti-cancer agents

- To evaluate PD of AZD5305 in tumour tissue when given orally as monotherapy

-Module 1: To characterize the PK of AZD5305 in plasma and urine, following a single dose and at steady state after multiple dosing, when given orally as monotherapy

-Module 2: To characterise the PK of AZD5305 and paclitaxel, following a single dose and at steady state after multiple dosing in plasma, when given in combination.

-Module 3: To characterise the PK of AZD5305, carboplatin +/- paclitaxel following a single dose and at steady state after multiple dosing in plasma, when given in combination

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1 Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
2 Age ≥ 18 at the time of screening
3 Patients must have histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment and meeting module specific eligibility criteria.
4 Eastern Cooperative Oncology Group Performance status (ECOG PS: 0-2)
5 Life expectancy ≥ 12 weeks
6 Progressive cancer at the time of study entry
7 Patients must have evaluable disease as per RECIST v1.1
8 Female subjects of childbearing potential:Must have negative pregnancy test result at screening and prior to each administration of study treatment and must use at least one highly effective method of birth control.
9 Female subjects must not breastfeed and must not donate or retrieve ova for their own use, from screening to approximately 6 months after the last dose of study treatment with IMP.
10 Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 6 months after the last dose of AZD5305 IMP.
11. Adequate organ and marrow function as defined by the protocol.
12. For expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour specimen is mandatory except if stated that it is optional in a specific Module.

E.4

Principal exclusion criteria

1 Treatment with any of the following:
(a) Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
(b) Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is longer) of the first dose of study treatment
(c) Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
(d) Any live virus or bacterial vaccine within 28 days of the first dose of study treatment
2 Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 (CYP3A4) strong and moderate inhibitors or inducers.
3 Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
4 Receiving continuous corticosteroids at a dose of >10 mg prednisone/day or equivalent for any reason.
5 Major surgery within 4 weeks of the first dose of study treatment.
6 Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
7 With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment.
8 Any history of persisting (> 2 weeks) severe pancytopenia due to any cause
9 Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of >10mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment
10 As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
11 Patients with any known predisposition to bleeding
12 Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTcF) > 450 milliseconds or QTcF<340 milliseconds
- Any factors that increase the risk of QT prolongation, shortening or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long or short QT syndrome, family history of long QT syndrome, familial short QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong or shorten the QT interval.
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG and clinically significant sinus node dysfunction not treated with pacemaker.
13 Other cardiovascular diseases as defined by any of the following:
(a) Symptomatic heart failure,
(b) uncontrolled hypertension,
(c) hypertensive heart disease with significant left ventricular hypertrophy
(d) acute coronary syndrome (ACS)/acute myocardial infarction (AMI), unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months.
(e) cardiomyopathy of any etiology
(f) presence of clinically significant valvular heart disease
(g) history of atrial or ventricular arrhythmia requiring treatment;
subjects with atrial fibrillation
and optimally controlled ventricular rate (<100 beats per minute)
are permitted

(h) subjects with atrial fibrillation and optimally controlled ventricular rate are permitted

(i) transient ischaemic attack, or stroke within 6 months prior to screening
(j) patients with symptomatic hypotension at screening
14 Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML).
15 Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305
16 Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s)
17 Any concurrent therapy anti-cancer therapy or concurrent use of prohibited medications
18 Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
19 Any condition that, in the opinion of the investigator, would interfere with evaluation of the study treatment or interpretation of subject safety or study results
20 Concurrent enrolment in another clinical study, unless it is an observational (non interventional) clinical study or during the follow-up period of an interventional study
21 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site
22 Previous study treatment assignment in the present study
23 Uncontrolled intercurrent illness within the last 12 months

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability will be assessed by the presence of AEs, SAEs, DLTs, and abnormal laboratory parameters, vital signs, and ECG results

E.5.1.1

Timepoint(s) of evaluation of this end point

From time of Informed Consent to 90 days post last dose

E.5.2

Secondary end point(s)

Secondary endpoints are:
- Plasma concentrations of AZD5305 and plasma PK parameters, including but not limited to AUC, Cmax and Tmax as data allow, of AZD5305 after single dose and multiple doses administration

- Radiological response evaluated according to response evaluation criteria in solid tumours (RECIST v1.1)
 - Best percentage change in target lesion
 - ORR, DoR, PFS, TTR

-For ovarian cancer patients, CA125 response evaluated according to the GCIG criteria
-For prostate cancer patients, PSA50 response and ORR and rPFS using RECIST 1.1 and PCWG3 criteria

- Includes, but is not limited to, assessment of modulation from baseline (Visit 1) or pretreatment in pH2AX (Ser139) PD biomarker.

-Plasma concentrations and PK parameters of AZD5305 and paclitaxel
after single dose and multiple doses administration, including, but not
limited to AUC, Cmax and Tmax, as data allow.

-Total plasma concentration and PK parameters, as data allow, of
carboplatin during and after infusion.

--Serum concentrations and PK parameters of T-DXd (T-DXd, total anti- HER2 antibody and MAAA-1181) after single dose and multiple dose
administration, including, but not limited to AUC, Cmax and Tmax, as
data allow.

E.5.2.1

Timepoint(s) of evaluation of this end point

All endpoints will be assessed from Day 1 of treatment through the end of treatment, with the exception of efficacy which will be assessed from screening through objective disease progression.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Dose escalation and dose expansion

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind